ARTHRITIS & RHEUMATISM
Vol. 56, No. 6, June 2007, pp 1966–1973
© 2007, American College of Rheumatology
Prevalence and Etiology of Low Bone Mineral Density in
Juvenile Systemic Lupus Erythematosus
Sandrine Compeyrot-Lacassagne, Pascal N. Tyrrell, Eshetu Atenafu, Andrea S. Doria,
Derek Stephens, David Gilday, and Earl D. Silverman
Objective. Studies of adults with systemic lupus
erythematosus (SLE) have frequently demonstrated the
presence of decreased bone mineral density (BMD).
However, there have been few investigations in pediatric
patients to date. This study was undertaken to deter-
mine the prevalence of low BMD in patients with
juvenile SLE and to identify associated risk factors.
Methods. We studied 64 consecutive patients with
juvenile SLE in whom routine dual x-ray absorptio-
metry (DXA) scanning was performed. Lumbar spine
osteopenia was defined as a BMD Z score of <?1 and
>?2.5, and osteoporosis as a BMD Z score of <?2.5.
Decreased hip BMD was defined as a value of <80%.
Data on disease activity, quality of life, disease-related
damage, sex, ethnicity, body mass index, age at diagno-
sis, age at DXA, medication use and duration, clinical
features, and puberty status were collected at the time of
Results. Lumbar spine osteopenia was seen in 24
patients (37.5%) and osteoporosis in 13 (20.3%). De-
creased hip BMD was present in 12 patients (18.8%). By
univariate analysis, osteopenia was significantly corre-
lated with age, disease duration, duration of cortico-
steroid use, cumulative corticosteroid dose, azathio-
prine use, cyclophosphamide use, lupus nephritis, and
damage. Two additional variables, mycophenolate
mofetil use and class III–IV nephritis, were associated
with osteoporosis. Abnormal hip BMD was associated
with disease duration, duration of corticosteroid use,
and cumulative corticosteroid dose. By multivariate
analysis, only disease duration remained in the model
for osteoporosis and abnormal hip BMD, while cumu-
lative corticosteroid dose was the variable associated
Conclusion. These results indicate that osteope-
nia and osteoporosis are common in juvenile SLE and
are associated more closely with increased disease du-
ration than with cumulative corticosteroid dose.
Juvenile systemic lupus erythematosus is a mul-
tisystem autoimmune condition characterized by chronic
inflammation and by the presence of autoantibodies.
Although patients with juvenile SLE comprise only
15–20% of all SLE patients, it has been suggested that
they have more severe disease than adults with SLE,
necessitating more frequent use of high-dose cortico-
steroids (1). Despite the more severe disease course of
juvenile SLE, however, there has been significant im-
provement in long-term mortality. Therefore, more
studies have focused on long-term morbidities, specifi-
cally, premature atherosclerosis and osteoporosis lead-
ing to insufficiency fractures (2–4).
Osteoporosis, an illness generally associated with
postmenopausal women, is characterized by loss of both
bone mass and microarchitectural integrity (5). One
crucial determinate in the development of osteoporosis
is the acquisition of appropriate peak mass in late
adolescence and early adulthood (6). A failure to
achieve adolescent peak bone mass may be associated
with premature osteoporosis and increased risk of frac-
ture. The development of peak bone mass is the result of
interactions between nutritional factors including cal-
cium intake, environmental exposures, physical activity,
and medications (7,8). Of particular concern with regard
to children with chronic rheumatic diseases are the
detrimental effects of chronic inflammation and cortico-
steroid use (9–13). These concerns are particularly im-
portant in juvenile SLE, since these patients tend to have
Sandrine Compeyrot-Lacassagne, MD, MSc, Pascal N. Tyr-
rell, MSc, Eshetu Atenafu, MSc, Andrea S. Doria, MD, PhD, Derek
Stephens, MSc, David Gilday, MD, Earl D. Silverman, MD: Hospital
for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Address correspondence and reprint requests to Earl D.
Silverman, MD, Division of Rheumatology, Hospital for Sick Children,
555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail:
Submitted for publication March 30, 2006; accepted in revised
form February 27, 2007.
severe chronic inflammation and frequently receive pro-
longed courses of high-dose corticosteroid therapy. De-
spite these concerns, there have been few studies exam-
ining osteoporosis and the development of fragility
fractures in patients with juvenile SLE (2,14–16). The
aim of the present study was to identify risk factors
associated with osteoporosis in this patient population.
PATIENTS AND METHODS
Patients. In January 2001, dual x-ray absorptiometry
(DXA) assessment became routine in the pediatric SLE clinic
at the Hospital for Sick Children. Sixty-four consecutive pa-
tients who fulfilled the American College of Rheumatology
(ACR) classification criteria for SLE (17), had onset of SLE
before the age of 18 years, and underwent DXA scanning
with lumbar spine osteoporosis, and patients with decreased hip BMD*
Demographic and disease characteristics and medication use in the total cohort and in patients with lumbar spine osteopenia, patients
(n ? 64)
Patients with osteopenia
(lumbar spine BMD
??1 and ??2.5)
(n ? 24)
Patients with osteo-
porosis (lumbar spine
(n ? 13)
Patients with hip
(n ? 12)
Female, no. (%)
Ethnicity, no. (%)†
Postpubertal, no. (%)
Body mass index, kg/m2
Age at disease onset, years
Disease duration, years
C-HAQ ?0, no. (%)
Adjusted mean SLEDAI
SDI ?0, no. (%)
Clinical features, no. (%)
Class III–IV nephritis
Medications used, no. (%)
Duration of medication use, days
Ever used, no. (%)
Current user, no. (%)
Prednisone, no. (%)
Methylprednisolone, no. (%)
Cumulative dose, gm/kg
Duration of use, years
14.3 ? 3.3
15.8 ? 2.8
16.6 ? 2.1
14.74 ? 3.68
22.2 ? 4.8
11.4 ? 3.4
2.9 ? 2.8
2.6 ? 2.3
4.6 ? 4.9
3.5 ? 3.1
22.3 ? 5.0
11.4 ? 3.6
4.4 ? 3.5
3.0 ? 2.4
4.9 ? 5.4
4.2 ? 3.6
23.2 ? 4.7
10.8 ? 4.2
5.8 ? 3.7
2.3 ? 1.2
4.1 ? 3.4
5.2 ? 3.8
22.3 ? 5.63
10.05 ? 3.48
4.69 ? 3.43
2.78 ? 2.73
4.33 ? 5.52
3.09 ? 3.23
634.9 ? 585.5
893.4 ? 815.9
409.3 ? 413.6
982.1 ? 90.1
1,101.3 ? 607.2
1,153.0 ? 937.3
380.2 ? 445.1
1,360.8 ? 1,117.5
1,330.0710.5 ? 876.1
2,008.8 ? 804.2
171 ? 185.8
1,546.3 ? 1,352.0
1,441.1 ? 1,032.6
380.2 ? 445.1
1,829.6 ? 1,238.9
319.5 ? 342.1
2.7 ? 2.6
506.2 ? 413.6
3.9 ? 3.2
626.9 ? 381.5
5.1 ? 3.4
560.9 ? 417.5
4.1 ? 2.9
* Except where indicated otherwise, values are the mean ? SD. BMD ? bone mineral density; SLE ? systemic lupus erythematosus; C-HAQ ?
Childhood Health Assessment Questionnaire; ECLAM ? European Consensus Lupus Activity Measurement; SLEDAI ? SLE Disease Activity
Index; SDI ? Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; CNS ? central nervous
system; NSAID ? nonsteroidal antiinflammatory drug.
† Ethnicity data were not available for some patients.
BMD IN JUVENILE SLE1967
between January 2001 and July 2004 were eligible for the
The medical records of these patients were reviewed
and information on the following parameters was extracted:
ethnicity, sex, body mass index (BMI) at the time of DXA, age
at diagnosis, age at the time of DXA, disease duration,
corticosteroid requirement (duration of corticosteroid use,
cumulative corticosteroid dose), requirement for and duration
of other medications (methotrexate, cyclophosphamide, hy-
droxychloroquine, cyclosporine, mycophenolate mofetil, and
azathioprine), clinical features (renal involvement including
World Health Organization classification, central nervous sys-
tem involvement, arthritis, serositis, and cutaneous involve-
ment), osteoporosis complications (vertebral fractures), pu-
berty status (pre- or postpubertal), quality of life (Childhood
Health Assessment Questionnaire ), damage score (dam-
age defined as a Systemic Lupus International Collaborating
Clinics/ACR Damage Index [SDI]  of ?0), disease activity
(scores on the SLE Disease Activity Index [SLEDAI]  and
European Consensus Lupus Activity Measure [ECLAM] )
at the time of DXA, and adjusted mean SLEDAI (22) during
6 months prior to the bone mineral density (BMD) assessment.
Calcium and vitamin D supplementation at the time of DXA
could not be accurately evaluated by chart review and there-
fore were not included in the analysis. Puberty status was
determined either by using Tanner stage when available (pu-
berty defined as Tanner stage ?4) or by determining whether
female patients had had their first menses prior to DXA. BMI
was defined as weight/height2. Ethnicity was divided into 5
groupings: African, Asian, Caucasian, Native Canadian, and
other (when ethnicity was mixed).
Determination of the average amount of physical
activity was not possible by chart review. None of the patients
were involved in any formal exercise program for osteoporosis.
The study was approved by the Research Ethics Board
of the Hospital for Sick Children.
BMD measurement. The first DXA scan performed on
each patient was chosen for study. All BMD measurements
were obtained with the same DXA instrument (Lunar Prodigy;
GE Lunar, Madison, WI). BMD was measured in the lumbar
spine (L2–L4) and in the femoral neck (mean value of the right
and left hips was used). The lumbar spine BMD values were
transformed into Z scores by comparing them with age- and
sex-specific reference values for this equipment (23–25). The
femoral neck BMD measurements were expressed as percent-
ages since the sample size used for the pediatric reference
values was not of sufficient magnitude to allow for use of a Z
score. We defined osteopenia as a lumbar spine BMD Z score
of ??1 and ??2.5, osteoporosis as a lumbar spine BMD Z
score of ??2.5, and decreased hip BMD as a BMD of ?80%.
Statistical analysis. Descriptive statistics were used to
assess the demographic variables. Pearson’s correlation coef-
ficient was used in univariate analysis to determine associa-
tions with osteopenia and osteoporosis. The chi-square test
and Fisher’s exact test were used as appropriate to examine
associations between dichotomous variables. Variables identi-
fied as significant in the univariate analysis were entered into
a logistic regression analysis. Statistical tests were performed
using SAS, version 8.2 (SAS Institute, Cary, NC). P values less
than 0.05 were considered significant.
The cohort consisted of 64 patients (49 girls and
15 boys) who had a DXA scan performed (Table 1).
DXA was performed a mean ? SD of 2.9 ? 2.8 years
following diagnosis; in 5 patients, DXA was performed
at presentation. Lumbar spine BMD was in the range of
osteopenia in 24 patients (37.5%) and in the range of
osteoporosis in 13 patients (20.3%). Twelve patients
(18.75%) had a mean hip BMD of ?80% (Table 1); the
lumbar spine BMD Z score was ??1 in 10 of these
patients and ??2.5 in 6. Clinical and laboratory char-
acteristics of the total cohort and of BMD subgroups are
shown in Table 1.
Univariate analysis. The clinical, laboratory, and
medication data were entered into univariate analyses
for osteopenia at the lumbar spine, osteoporosis at the
lumbar spine, and mean hip BMD ?80%. This analysis
revealed that osteopenia was associated with the age of
the patient at the time of DXA, disease duration,
duration of corticosteroid therapy, cumulative cortico-
steroid dose, azathioprine use, cyclophosphamide use,
history of nephritis, and presence of damage (SDI ?0)
(Table 2). Osteoporosis was associated with the age of
the patient at the time of DXA, disease duration,
duration of corticosteroid therapy, cumulative cortico-
steroid dose, azathioprine use, mycophenolate mofetil
use, cyclophosphamide use, history of nephritis, renal
biopsy showing class III–IV lupus nephritis, and pres-
ence of damage (Table 2). Mean hip BMD ?80% was
associated with disease duration, duration of cortico-
steroid use, and cumulative corticosteroid dose (Table
2). Of note, we did not find that any statistically signif-
icant associations between scores on any of the measures
of disease activity (SLEDAI, ECLAM, adjusted mean
SLEDAI) and either osteopenia or osteoporosis at the
lumbar spine or hip BMD ?80%.
Multivariate analysis. Values that were statisti-
cally significantly associated with lumbar spine osteope-
nia, lumbar spine osteoporosis, and/or decreased hip
BMD were entered separately into regression analyses.
Our initial analysis (Pearson’s correlation test) revealed
that duration of corticosteroid use, disease duration, and
age at the time of DXA were highly correlated, making
the model unstable (Table 3). Disease duration and
duration of corticosteroid use were particularly interre-
lated, with a Pearson correlation coefficient of 0.97 (P
?0.0001) (Table 3). As a result of this finding, 3 separate
analyses were performed using 2 of these 3 variables at
a time, for lumbar spine osteopenia, lumbar spine
osteoporosis, and mean hip BMD ?80%. The best
1968 COMPEYROT-LACASSAGNE ET AL
models for each cutoff are shown in Table 4. Cumulative
corticosteroid dose was significantly associated with
lumbar spine osteopenia, while disease duration best
predicted both lumbar spine osteoporosis and mean hip
BMD ?80%. The association between nephritis and
lumbar spine osteoporosis approached statistical signif-
icance (P ? 0.0541) (Table 4).
Further analysis of the statistically significant
parameters confirmed the validity of the models, since
odds ratio point estimates were ?1 with confidence
intervals excluding 1. The results of this analysis con-
firmed that cumulative corticosteroid dose was signifi-
cantly associated with lumbar spine osteopenia and that
disease duration best predicted both lumbar spine osteo-
porosis and mean hip BMD ?80% (Table 5). This
analysis also showed that the association between lupus
nephritis and lumbar spine osteoporosis was not statis-
tically significant but approached significance.
Osteoporosis is a systemic skeletal disorder char-
acterized by low bone mass and microarchitectural de-
terioration of bone tissue, leading to increased bone
fragility and fracture (26). Although osteoporosis is a
well-known complication of adult-onset SLE, few studies
have been performed in juvenile SLE (2,14–16). In
contrast to studies of juvenile dermatomyositis (11) and
juvenile idiopathic arthritis (9,12,13,27,28), which have
shown decreased BMD in these patients, only 2 of 4
studies of juvenile SLE demonstrated decreased BMD
(14,16). In this study, we found that osteopenia and
osteoporosis at the lumbar spine and low hip BMD were
common in patients with juvenile SLE, occurring in
38%, 20%, and 19% of patients, respectively. The major
difference between our study and previous investigations
in juvenile SLE is that the sample size of pediatric
patients in our study was larger than those in the earlier
studies in which lower BMD in patients with juvenile
SLE was also demonstrated (14, 16). Consistent with our
results were the findings of 2 studies of patients who
were ?19 years old at the time of study but whose SLE
had begun during childhood, both of which demon-
strated decreased BMD (2,14). While the frequency of
osteopenia was comparable (14), the frequency of osteo-
Multivariate analysis results*
Correlation with lumbar spine
BMD ??1 and ??2.5
Correlation with lumbar spine
Correlation with hip BMD ?80%
Cumulative corticosteroid dose
Disease duration (0.0028), lupus
Disease duration (0.0249)
* Three separate multivariate analyses using 2 of 3 interrelated
variables at a time were performed. All variables that were statistically
significant in univariate analysis were entered into the regression
analysis. BMD ? bone mineral density.
Univariate analysis of clinical variables and medications*
Lumbar spine BMD
??1 and ??2.5
Lumbar spine BMD
Age at time of DXA
Duration of corticosteroid use
Cumulative corticosteroid dose
Mycophenolate mofetil use
Class III or IV lupus nephritis
* All variables listed in Table 1 were tested; only the statistically significant variables are shown here.
BMD ? bone mineral density; DXA ? dual x-ray absorptiometry; SDI ? Systemic Lupus International
Collaborating Clinics/American College of Rheumatology Damage Index.
variables assessed in pairs
Pearson’s correlation coefficients between 3 interrelated
Age at time of DXA/disease duration*
Age at time of DXA/duration of cortico-
Disease duration/duration of cortico-
* DXA ? dual x-ray absorptiometry.
BMD IN JUVENILE SLE1969
porosis was higher in our study, in which the population
was exclusively pediatric.
Because the results of previous work in adults
with SLE have suggested that both chronic inflammation
and corticosteroid therapy are associated with decreased
BMD, we examined the contributions of these factors to
osteopenia and osteoporosis in order to better under-
stand the pathogenesis of decreased BMD in patients
with juvenile SLE. We did not find that the cumulative
dose of corticosteroids or duration of corticosteroid use
was an important predictor of lumbar spine osteoporosis
or hip BMD ?80%. However, cumulative corticosteroid
dose was associated with lumbar spine osteopenia by
multivariate analysis, although the low odds ratio sug-
gested that the contribution was minor.
Two previous studies in juvenile SLE showed that
BMD was correlated with cumulative corticosteroid
dose, but the study populations included adults with
childhood-onset SLE, as well as children (2,14). Consis-
tent with our findings are the results of studies in adult
premenopausal patients with SLE, in which decreased
BMD was not found to be correlated with corticosteroid
use, total corticosteroid dose, or duration of cortico-
steroid use (29–37). Investigations of pediatric patients
with nephrotic syndrome have yielded conflicting results
regarding the role of corticosteroids in the development
of osteoporosis (38,39). One reason for the disparate
findings regarding the role of corticosteroids in osteo-
porosis might relate to the fact that prolonged high-dose
steroid therapy may lead to increases in weight and BMI,
which may be associated with secondary improvement of
spinal bone mineral content. Further studies are needed
to confirm our findings of the lack of association of
osteoporosis with corticosteroid use in juvenile SLE.
Studies in adults with SLE have suggested that
the decreased BMD is related to disease damage and
disease duration, rather than to measures of disease
activity or severity (30,32–34,36). In the present study,
univariate analysis showed multiple measures of disease
activity, specific disease manifestations, and therapies to
be associated with the 3 measures of abnormally low
BMD. However, multivariate analysis revealed that only
disease duration was associated with lumbar spine osteo-
porosis and decreased hip BMD. The only measure of
disease activity that approached statistical significance
was the association of lupus nephritis as a predictor of
lumbar spine osteoporosis. The role of this variable must
be analyzed carefully and may require further study.
Interestingly, whether the nephritis was active or inac-
tive at the time of BMD measurement did not affect this
finding. Previous studies of patients with juvenile SLE
failed to show a relationship between BMD and mea-
sures of disease activity, severity, or damage (2,14–16).
Consistent with studies in adults with SLE
(33,34), we did not find that scores on global measures of
disease activity, including the SLEDAI, ECLAM, and
adjusted mean SLEDAI, were significantly associated
with low BMD, despite evidence that these indices are
good measures of disease activity in juvenile SLE (40–
42). Although we found that many surrogate measures
of disease severity, including use of immunosuppressive
agents and disease damage score (as measured by SDI),
were significantly associated with BMD by univariate
analysis, none of these measures was significantly asso-
ciated with BMD by multivariate analysis. Our finding of
a lack of association with measures of disease damage in
multivariate analysis contrasts with the results of studies
in adult SLE (30,32–34,36). Our results suggest that
factors other than disease damage or severity may be
more important in determining BMD in juvenile SLE.
However, these findings might also be explained by a
lack of power in our analysis, given the sample size.
To date, there has not been a standard way of
describing BMD results or defining osteopenia and
osteoporosis in pediatric patients with rheumatic dis-
eases (2,16). Definitions of osteopenia and osteoporosis
in adults (43) have been validated by epidemiologic
studies correlating each standard deviation decrease in
BMD with an increase of fracture risk, in postmeno-
pausal women (44–46). The validity of using Z scores
and definitions of adult osteopenia and osteoporosis in
pediatric patients has been demonstrated in a study of
patients with juvenile dermatomyositis (47). In the
present work we report lumbar spine BMD as Z scores
since these values were available for this site in our
patients. Hip BMD is reported as percentages, since
validated Z scores were not available. At our institution,
Results of the final models (multivariate analysis)*
Variable (OR point estimate
[Wald’s 95% CI])
Correlation with lumbar spine
BMD ??1 and ??2.5
Correlation with lumbar spine
Cumulative corticosteroid dose
Disease duration (1.599
lupus nephritis (8.788
Disease duration (1.290
Correlation with hip BMD
* The statistical significance of the models identified in the multivar-
iate analysis was further analyzed, and the validity of the models was
confirmed. OR ? odds ratio; 95% CI ? 95% confidence interval;
BMD ? bone mineral density.
1970 COMPEYROT-LACASSAGNE ET AL
hip BMD of 80–90% is considered a mild decrease
(equivalent to a Z score of approximately ?1 to ?2 in
adults), 70–80% a moderate decrease, and ?70% a
marked decrease. Therefore, we chose 80% (0.8) as a
cutoff for defining abnormal hip BMD in the present
study. We suggest that in general, the definitions of
osteopenia and osteoporosis used in adults, i.e., scores of
??1 and ??2.5, respectively, should be used in patients
with pediatric rheumatic diseases. However, a large
collaborative study is needed to confirm that these
cutoffs define increased risk of fracture in children, as
has been done in postmenopausal women.
A limitation of our study was the use of BMD,
which does not take into account structural properties of
bone (5,25). It would have been of benefit to have data
regarding microarchitecture and mineralization of the
bones, but we could not justify performing bone biopsy,
nor did we have access to quantitative measures ob-
tained by computed tomography or magnetic resonance
imaging. However, DXA data can be readily extrapo-
lated to clinical practice. Another limitation of our study
was the lack of data on calcium and vitamin D intake,
due to the retrospective design of the study. Although
calcium supplementation has been shown to be of
benefit in maintaining normal BMD increase in healthy
prepubertal children (7), studies of children with rheu-
matic diseases have yielded conflicting results (14,16,48–
50). Similarly, we did not evaluate the effect of activity
on BMD, due to the retrospective study design. Al-
though regular exercise is known to increase BMD in
healthy children (51–53), studies in patients with pedi-
atric rheumatic diseases have had conflicting results
(16,28). Prospective studies are needed to determine the
effects of calcium and vitamin D intake and exercise on
BMD and fracture risk in juvenile SLE.
Our study demonstrated rates of osteopenia and
osteoporosis at the lumbar spine of 38% and 20%,
respectively, and a 19% rate of decreased hip BMD.
These findings are similar to those in previous investi-
gations of adult SLE (29–37). We suggest that, pending
future studies examining the association of fracture risk
and BMD in pediatric patients, the definitions of os-
teopenia and osteoporosis used in adults, i.e., ?1 and
?2.5, respectively, should be used. Disease duration and
possibly lupus nephritis (not necessarily active at the
time of DXA) were identified as predictors of low BMD,
suggesting that patients with juvenile SLE, and in par-
ticular those with nephritis, are at risk of osteoporosis
and possibly fracture. However, since the long-term
safety of antiresorptive agents has not been established
in pediatric patients, we do not advocate the routine use
of these agents to prevent osteoporosis in children with
longstanding SLE. Long-term studies are needed to
determine the morbidity associated with osteoporosis in
juvenile SLE and the role of prophylactic therapy to
prevent this complication.
Dr. Silverman had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy of the
Study design. Compeyrot-Lacassagne, Gilday, Silverman.
Acquisition of data. Compeyrot-Lacassagne, Tyrrell, Gilday, Silver-
Analysis and interpretation of data. Compeyrot-Lacassagne, Tyrrell,
Atenafu, Doria, Stephens, Silverman.
Manuscript preparation. Compeyrot-Lacassagne, Tyrrell, Atenafu,
Statistical analysis. Atenafu, Stephens.
1. Rood MJ, ten Cate R, van Suijlekom-Smit LW, den Ouden EJ,
Ouwerkerk FE, Breedveld FC, et al. Childhood-onset systemic
lupus erythematosus: clinical presentation and prognosis in 31
patients. Scand J Rheumatol 1999;28:222–6.
2. Trapani S, Civinini R, Ermini M, Paci E, Falcini F. Osteoporosis in
juvenile systemic lupus erythematosus: a longitudinal study on the
effect of steroids on bone mineral density. Rheumatol Int 1998;
3. Falaschi F, Ravelli A, Martignoni A, Migliavacca D, Sartori M,
Pistorio A, et al. Nephrotic-range proteinuria, the major risk factor
for early atherosclerosis in juvenile-onset systemic lupus erythem-
atosus. Arthritis Rheum 2000;43:1405–9.
4. Posadas-Romero C, Torres-Tamayo M, Zamora-Gonzalez J,
Aguilar-Herrera BE, Posadas-Sanchez R, Cardoso-Saldana G, et
al. High insulin levels and increased low-density lipoprotein oxi-
dizability in pediatric patients with systemic lupus erythematosus.
Arthritis Rheum 2004;50:160–5.
5. Roth J, Palm C, Scheunemann I, Ranke MB, Schweizer R,
Dannecker GE. Musculoskeletal abnormalities of the forearm in
patients with juvenile idiopathic arthritis relate mainly to bone
geometry. Arthritis Rheum 2004;50:1277–85.
6. Rabinovich CE. Bone mineral status in juvenile rheumatoid
arthritis. J Rheumatol Suppl 2000;58:34–7.
7. Johnston CC Jr, Miller JZ, Slemenda CW, Reister TK, Hui S,
Christian JC, et al. Calcium supplementation and increases in
bone mineral density in children. N Engl J Med 1992;327:82–7.
8. Slemenda CW, Reister TK, Hui SL, Miller JZ, Christian JC,
Johnston CC Jr. Influences on skeletal mineralization in children
and adolescents: evidence for varying effects of sexual maturation
and physical activity. J Pediatr 1994;125:201–7.
9. Pepmueller PH, Cassidy JT, Allen SH, Hillman LS. Bone miner-
alization and bone mineral metabolism in children with juvenile
rheumatoid arthritis. Arthritis Rheum 1996;39:746–57.
10. Perez MD, Abrams SA, Loddeke L, Shypailo R, Ellis KJ. Effects
of rheumatic disease and corticosteroid treatment on calcium
metabolism and bone density in children assessed one year after
diagnosis, using stable isotopes and dual energy x-ray absorptio-
metry. J Rheumatol Suppl 2000;58:38–43.
11. Stewart WA, Acott PD, Salisbury SR, Lang BA. Bone mineral
density in juvenile dermatomyositis: assessment using dual x-ray
absorptiometry. Arthritis Rheum 2003;48:2294–8.
BMD IN JUVENILE SLE1971
12. Kotaniemi A, Savolainen A, Kroger H, Kautiainen H, Isomaki H.
Weight-bearing physical activity, calcium intake, systemic glu-
cocorticoids, chronic inflammation, and body constitution as de-
terminants of lumbar and femoral bone mineral in juvenile chronic
arthritis. Scand J Rheumatol 1999;28:19–26.
13. Henderson CJ, Cawkwell GD, Specker BL, Sierra RI, Wilmott
RW, Campaigne BN, et al. Predictors of total body bone mineral
density in non–corticosteroid-treated prepubertal children with
juvenile rheumatoid arthritis. Arthritis Rheum 1997;40:1967–75.
14. Lilleby V, Lien G, Frey Froslie K, Haugen M, Flato B, Forre O.
Frequency of osteopenia in children and young adults with child-
hood-onset systemic lupus erythematosus. Arthritis Rheum 2005;
15. Castro TC, Terreri MT, Szejnfeld VL, Castro CH, Fisberg M,
Gabay M, et al. Bone mineral density in juvenile systemic lupus
erythematosus. Braz J Med Biol Res 2002;35:1159–63.
16. Alsufyani KA, Ortiz-Alvarez O, Cabral DA, Tucker LB, Petty RE,
Nadel H, et al. Bone mineral density in children and adolescents
with systemic lupus erythematosus, juvenile dermatomyositis, and
systemic vasculitis: relationship to disease duration, cumulative
corticosteroid dose, calcium intake, and exercise. J Rheumatol
17. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield
NF, et al. The 1982 revised criteria for the classification of systemic
lupus erythematosus. Arthritis Rheum 1982;25:1271–7.
18. Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of
health status in children with juvenile rheumatoid arthritis. Arthri-
tis Rheum 1994;37:1761–9.
19. Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E,
Gordon C, et al. The reliability of the Systemic Lupus Interna-
tional Collaborating Clinics/American College of Rheumatology
Damage Index in patients with systemic lupus erythematosus.
Arthritis Rheum 1997;40:809–13.
20. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang DH,
and the Committee on Prognosis Studies in SLE. Derivation of the
SLEDAI: a disease activity index for lupus patients. Arthritis
21. Vitali C, Bencivelli W, Isenberg DA, Smolen JS, Snaith ML, Sciuto
M, et al, and The European Consensus Study Group for Disease
Activity in SLE. Disease activity in systemic lupus erythematosus:
report of the Consensus Study Group of the European Workshop
for Rheumatology Research. II. Identification of the variables
indicative of disease activity and their use in the development of an
activity score. Clin Exp Rheumatol 1992;10:541–7.
22. Ibanez D, Urowitz MB, Gladman DD. Summarizing disease
features over time. I. Adjusted mean SLEDAI derivation and
application to an index of disease activity in lupus. J Rheumatol
23. Wacker W, Barden HS. Pediatric reference data for male and
female total body and spine BMD and BMC [abstract]. Meeting of
the International Society of Clinical Densitometry; 2002; Dallas.
24. Genant HK. Universal standardization for dual X-ray absorptio-
metry: patient and phantom cross-calibration results. J Bone
Miner Res 1995;10:997–8.
25. Bhudhikanok GS, Wang MC, Eckert K, Matkin C, Marcus R,
Bachrach LK. Differences in bone mineral in young Asian and
Caucasian Americans may reflect differences in bone size. J Bone
Miner Res 1996;11:1545–56.
26. Consensus Development Conference. Prophylaxis and treatment
of osteoporosis. Osteoporos Int 1991;1:114–117.
27. Lien G, Flato B, Haugen M, Vinje O, Sorskaar D, Dale K, et al.
Frequency of osteopenia in adolescents with early-onset juvenile
idiopathic arthritis: a long-term outcome study of one hundred five
patients. Arthritis Rheum 2003;48:2214–23.
28. Lien G, Selvaag AM, Flato B, Haugen M, Vinje O, Sorskaar D, et
al. A two-year prospective controlled study of bone mass and bone
turnover in children with early juvenile idiopathic arthritis. Arthri-
tis Rheum 2005;52:833–40.
29. Formiga F, Moga I, Nolla JM, Pac M, Mitjavila F, Roig-Escofet D.
Loss of bone mineral density in premenopausal women with
systemic lupus erythematosus. Ann Rheum Dis 1995;54:274–6.
30. Chen CJ, Yen JH, Tsai WC, Lin MB, Hsu SC, Tsai JJ, et al.
Decreased bone mineral density in premenopausal patients with
systemic lupus erythematosus. Kaohsiung J Med Sci 1996;12:
31. Kipen Y, Buchbinder R, Forbes A, Strauss B, Littlejohn G,
Morand E. Prevalence of reduced bone mineral density in systemic
lupus erythematosus and the role of steroids. J Rheumatol 1997;
32. Li EK, Tam LS, Young RP, Ko GT, Li M, Lau EM. Loss of bone
mineral density in Chinese pre-menopausal women with systemic
lupus erythematosus treated with corticosteroids. Br J Rheumatol
33. Becker A, Fischer R, Scherbaum WA, Schneider M. Osteoporosis
screening in systemic lupus erythematosus: impact of disease
duration and organ damage. Lupus 2001;10:809–14.
34. Bhattoa HP, Bettembuk P, Balogh A, Szegedi G, Kiss E. Bone
mineral density in women with systemic lupus erythematosus. Clin
35. Pineau CA, Urowitz MB, Fortin PJ, Ibanez D, Gladman DD.
Osteoporosis in systemic lupus erythematosus: factors associated
with referral for bone mineral density studies, prevalence of
osteoporosis and factors associated with reduced bone density.
36. Lee C, Almagor O, Dunlop DD, Manzi S, Spies S, Chadha AB, et
al. Disease damage and low bone mineral density: an analysis of
women with systemic lupus erythematosus ever and never receiv-
ing corticosteroids. Rheumatology (Oxford) 2006;45:53–60.
37. Bultink IE, Lems WF, Kostense PJ, Dijkmans BA, Voskuyl AE.
Prevalence of and risk factors for low bone mineral density and
vertebral fractures in patients with systemic lupus erythematosus.
Arthritis Rheum 2005;52:2044–50.
38. Lettgen B, Jeken C, Reiners C. Influence of steroid medication on
bone mineral density in children with nephrotic syndrome. Pediatr
39. Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ,
Stallings VA. Long-term, high-dose glucocorticoids and bone
mineral content in childhood glucocorticoid-sensitive nephrotic
syndrome. N Engl J Med 2004;351:868–75.
40. Brunner HI, Feldman BM, Bombardier C, Silverman ED. Sensi-
tivity of the Systemic Lupus Erythematosus Disease Activity
Index, British Isles Lupus Assessment Group Index, and Systemic
Lupus Activity Measure in the evaluation of clinical change in
childhood-onset systemic lupus erythematosus. Arthritis Rheum
41. Brunner HI, Silverman ED, Bombardier C, Feldman BM. Euro-
pean Consensus Lupus Activity Measurement is sensitive to
change in disease activity in childhood-onset systemic lupus ery-
thematosus. Arthritis Rheum 2003;49:335–41.
42. Brunner HI, Silverman ED, To T, Bombardier C, Feldman BM.
Risk factors for damage in childhood-onset systemic lupus ery-
thematosus: cumulative disease activity and medication use pre-
dict disease damage. Arthritis Rheum 2002;46:436–44.
43. Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev
N. The diagnosis of osteoporosis. J Bone Miner Res 1994;9:
44. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J,
Ensrud K, et al, for the Study of Osteoporotic Fractures Research
Group. Bone density at various sites for prediction of hip frac-
tures. Lancet 1993;341:72–5.
45. Johnston CC Jr, Slemenda CW, Melton LJ III. Clinical use of bone
densitometry. N Engl J Med 1991;324:1105–9.
1972 COMPEYROT-LACASSAGNE ET AL
46. Kanis JA, for the WHO Study Group. Assessment of fracture risk Download full-text
and its application to screening for postmenopausal osteoporosis:
synopsis of a WHO report. Osteoporos Int 1994;4:368–81.
47. Ellis KJ, Shypailo RJ, Hardin DS, Perez MD, Motil KJ, Wong
WW, et al. Z score prediction model for assessment of bone
mineral content in pediatric diseases. J Bone Miner Res 2001;16:
48. Reed A, Haugen M, Pachman LM, Langman CB. 25-hydroxy-
vitamin D therapy in children with active juvenile rheumatoid
arthritis: short-term effects on serum osteocalcin levels and bone
mineral density. J Pediatr 1991;119:657–60.
49. Warady BD, Lindsley CB, Robinson FG, Lukert BP. Effects of
nutritional supplementation on bone mineral status of children
with rheumatic diseases receiving corticosteroid therapy. J Rheu-
50. Lanou AJ, Berkow SE, Barnard ND. Calcium, dairy products, and
bone health in children and young adults: a reevaluation of the
evidence. Pediatrics 2005;115:736–43.
51. Mackelvie KJ, McKay HA, Khan KM, Crocker PR. Lifestyle risk
factors for osteoporosis in Asian and Caucasian girls. Med Sci
Sports Exerc 2001;33:1818–24.
52. Morris FL, Naughton GA, Gibbs JL, Carlson JS, Wark JD.
Prospective ten-month exercise intervention in premenarcheal
girls: positive effects on bone and lean mass. J Bone Miner Res
53. Bradney M, Pearce G, Naughton G, Sullivan C, Bass S, Beck T,
et al. Moderate exercise during growth in prepubertal boys:
changes in bone mass, size, volumetric density, and bone
strength; a controlled prospective study. J Bone Miner Res
BMD IN JUVENILE SLE1973